Substantial attention has been directed to synthesizing interesting molecules such as peptides, drugs, enzymes, catalysts, functional organic materials and ligands for biological receptors by preparing large random biological libraries. Such libraries are often based on using microorganisms. Each microorganism synthesizes one type of molecule, and a large chemical diversity is achieved by employing libraries containing a large number of microorganisms. The most used microorganisms for preparing libraries are yeast and bacteriophages. In the particular case of bacteriophages, also called phages, the molecule of interest can be displayed at the surface of the phage. Inside the phage resides the oligonucleotide sequence (the gene) that encodes for the displayed protein. This makes bacteriophages a very convenient tool for preparing and screening libraries because when an interaction is found between the molecule of interest and a target, the structure of the molecule can be deciphered by sequencing the gene encoding it. Unfortunately, screening a particular molecule of interest in the library can be very difficult. For example, one method currently employed to screen for a particular type of phage entails adding a phage library to a microtiter plate well that is coated with a receptor capable of attaching to a particular type of phage. After allowing a portion of the phages to bind to the receptor, either specifically or non-specifically, the unbound phages can be removed through washing. The bound receptors can then be recovered and copied to increase their numbers. The foregoing selection method can be repeated until genetic sequences show consensus. Several screening rounds can be required since a library can contain billions of different phages, each expressing a unique library element.
Biologically inspired approaches have been developed for improving the screening of viruses in a library. These approaches provide for the self-assembly or directed assembly of viruses such as bateriophages (i.e., viruses that infect bacteria) in an array using chemical linkers, nucleic acid hybridization, or metal ions. The filamentous M13 bacteriophage virus, in particular, has shown a tremendous capacity for incorporating biological and inorganic materials (including metallic, magnetic, and semi-conducting) into its self-assembled, genetically-modifiable architecture. Macroscopic organization of M13 bacteriophages has been achieved using liquid crystalline phase separation phenomena and virus-membrane complexes, creating materials of high uniformity and element density.
Unfortunately, current self-assembly and directed assembly methods often face a trade off between specificity and generality of the approach. The use of highly specific antibody interactions, however, has remained relatively unexplored due to the gross loss of antibody activity during sample preparation and processing. Soft lithographic methods, including microcontact printing, have been successful in maintaining the biomolecular activities of antibodies but are limited in feature size and pitch due to the mechanical properties of the elastomeric materials used in the printing of the antibodies.